Immediate Post-operative Enterocyte Injury, as Determined by Increased Circulating Intestinal Fatty Acid Binding Protein, Is Associated With Subsequent Development of Necrotizing Enterocolitis After Infant Cardiothoracic Surgery.
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Objectives: 1 Measure serial serum intestinal fatty acid binding protein levels in infants undergoing cardiac surgery with cardiopulmonary bypass to evaluate for evidence of early post-operative enterocyte injury. 2 Determine the association between immediate post-operative circulating intestinal fatty acid binding protein levels and subsequent development of necrotizing enterocolitis. Design: Observational cohort study. Intestinal fatty acid binding protein was measured pre-operatively, at rewarming, and at 6 and 24 h post-operatively. Percent of goal enteral kilocalories on post-operative day 5 and episodes of necrotizing enterocolitis were determined. Multivariable analysis assessed for factors independently associated with clinical feeding outcomes and suspected/definite necrotizing enterocolitis. Setting: Quaternary free-standing children's hospital pediatric cardiac intensive care unit. Patients: 103 infants <120 days of age undergoing cardiothoracic surgery with cardiopulmonary bypass. Interventions: None. Results: Median pre-operative intestinal fatty acid binding protein level was 3.93 ng/ml (range 0.24-51.32). Intestinal fatty acid binding protein levels rose significantly at rewarming (6.35 ng/ml; range 0.54-56.97; p = 0.008), continued to rise slightly by 6 h (6.57 ng/ml; range 0.75-112.04; p = 0.016), then decreased by 24 h (2.79 ng/ml; range 0.03-81.74; p < 0.0001). Sixteen subjects (15.7%) developed modified Bell criteria Stage 1 necrotizing enterocolitis and 9 subjects (8.8%) developed Stage 2 necrotizing enterocolitis. Infants who developed necrotizing enterocolitis demonstrated a significantly higher distribution of intestinal fatty acid binding protein levels at both 6 h (p = 0.005) and 24 h (p = 0.005) post-operatively. On multivariable analysis, intestinal fatty acid binding protein was not associated with percentage of goal enteral kilocalories delivered on post-operative day 5. Higher intestinal fatty acid binding protein was independently associated with subsequent development of suspected/definite necrotizing enterocolitis (4% increase in odds of developing necrotizing enterocolitis for each unit increase in intestinal fatty acid binding protein; p = 0.0015). Conclusions: Intestinal fatty acid binding protein levels rise following infant cardiopulmonary bypass, indicating early post-operative enterocyte injury. Intestinal fatty acid binding protein was not associated with percent of goal enteral nutrition achieved on post-operative day 5, likely due to protocolized feeding advancement based on clinically observable factors. Higher intestinal fatty acid binding protein at 6 h post-operatively was independently associated with subsequent development of necrotizing enterocolitis and may help identify patients at risk for this important complication.
Published Version (Please cite this version)
Watson, John D, Tracy T Urban, Suhong S Tong, Jeanne Zenge, Ludmilla Khailova, Paul E Wischmeyer and Jesse A Davidson (2020). Immediate Post-operative Enterocyte Injury, as Determined by Increased Circulating Intestinal Fatty Acid Binding Protein, Is Associated With Subsequent Development of Necrotizing Enterocolitis After Infant Cardiothoracic Surgery. Frontiers in pediatrics, 8. p. 267. 10.3389/fped.2020.00267 Retrieved from https://hdl.handle.net/10161/21093.
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Paul Wischmeyer M.D., EDIC, FASPEN, FCCM is a nutrition, exercise, critical care, and perioperative physician-researcher who specializes in enhancing preparation and recovery from surgery, critical care and COVID-19. He serves as a Tenured Professor of Anesthesiology and Surgery at Duke. He also serves as the Associate Vice Chair for Clinical Research in the Dept. of Anesthesiology and Director of the TPN/Nutrition Team at Duke. Dr. Wischmeyer earned his medical degree with honors at The University of Chicago Pritzker School of Medicine, where he was elected into the honor society of Alpha Omega Alpha for outstanding academic achievement. He completed his pediatric internship at University of Colorado Children’s Hospital and his anesthesiology/critical care residency training at the University of Chicago. He also completed a Clinical Pharmacology fellowship and the NIH K30 Clinical Research Scientist Training Program while at University of Chicago.
Dr. Wischmeyer’s clinical and research focus is in critical care, perioperative care exercise, and nutrition to help patients prepare and recover from illness and surgery. His research interests include surgical and ICU nutrition and exercise rehabilitation; role of parenteral, enteral, and oral nutrition to improve patient outcomes; perioperative optimization; post-illness muscle mass and functional recovery; and probiotics/microbiome. His research interests have also recently been focused on COVID-19 research into COVID-19 metabolism, role of probiotics in COVID19 prevention and treatment, and exercise and nutrition programs to recover from COVID-19 and Long COVID-19. Dr. Wischmeyer’s research group has been awarded multiple NIH, DOD, and other peer reviewed grants to perform research ranging from basic mechanistic cell work to large-scale multi-center clinical trials in the fields of critical care, perioperative medicine, nutrition, illness metabolism, microbiome/probiotics, and exercise interventions to improve functional outcomes. For his research work and clinical work, Dr. Wischmeyer has received numerous awards from national and international societies including, The Jeffrey Silverstein Award and Memorial Lecture for Humanism in Medicine from the American Delirium Society, The John M. Kinney Award for the most significant contribution to field of general nutrition, the Stanley Dudrick Research Scholar Award by the American Society for Parenteral and Enteral Nutrition and The Lifetime Achievement Award of the International Parenteral Nutrition Society (IPENEMA) for significant contributions to the field of nutrition. Dr. Wischmeyer has over 200 peer-reviewed publications in critical care, anesthesiology, and nutrition, including in the New England Journal of Medicine. Finally, he has been an invited speaker at numerous national and international medical meetings delivering over 900 invited presentations over his career. He has an H-index of 73 with over 16,500 citations to his work, including 1 publication with > 1000 citations and 55 publications with > 100 citations. He is also the founder and director of the Duke Online Clinical Nutrition Fellowship, an international fellowship to provide clinical nutrition training to healthcare providers worldwide, as well as unique scholarship opportunities for healthcare providers in developing nations.
Dr. Wischmeyer passion for helping patients recover from illness and surgery arises from his personal experiences as both doctor and patient in the ICU. Dr. Wischmeyer has undergone over 27 major surgeries and personally experienced multiple ICU stays due to a childhood GI illness that took more than half of his intestinal tract. Thus, preparation for surgery/critical care and recovery from illness are a way of life for Dr. Wischmeyer that he is passionate about teaching his patients and other caregivers worldwide.
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